1. General anesthetics

2. Objectives Define sleep, amnesia, analgesia, general anesthesia
List different phases/planes of GA
Classify the agents used for general anesthesia
Describe the mechanism of action, pharmacokinetics, therapeutics and adverse effects and drug interactions of different anesthetic drugs
Compare the pharmacological effects of thiopental sodium, propofol, and ketamine

3. Surgery Before Anesthesia50

4. Fun and Frolics led to Early Anesthesia50

5. What are General Anesthetics?
A drug that brings about a reversible loss of consciousness
generally administered by an anesthesiologist in order to induce or maintain general anesthesia to facilitate surgery.
Can be viewed as a pharmacological intervention used to prevent psychological and somatic adverse effects of surgical trauma and also to create convenient conditions for surgery.

6. General Anaesthesia (GA)
unconsciousness
amnesia
analgesia.
A variety of drugs are given to the patient that have different effects with the overall aim of ensuring unconsciousness, amnesia and analgesia.

7. Stages Of General Anesthesia
Stage I: Disorientation, altered consciousness
Stage II: Excitatory stage, delirium, uncontrolled movement, irregular breathing. Goal is to move through this stage as rapidly as possible.
Stage III: Surgical anesthesia; return of regular respiration.
Plane 3: Deep anesthesia. Shallow breathing, assisted ventilation needed. Level of anesthesia for painful surgeries
Plane 4: Diaphragmatic respiration only, assisted ventilation is required. Cardiovascular impairment.
Stage IV: Too deep; essentially an overdose and represents anesthetic crisis. This is the stage between respiratory arrest and death due to circulatory collapse.

8. Anesthetics divide into 2 classes
Inhalation Anesthetics
Gasses or Vapors
Usually Halogenated
Intravenous Anesthetics
Injections
Anesthetics or induction agents

9. Anesthetics divide into 2 classes
Inhalation Anesthetics
Gasses or Vapors
Usually Halogenated
Intravenous Anesthetics
Injections
Anesthetics or induction agents

10. Inhalation Anesthetics
Nitrous oxide
Halothane
Isoflurane
Sevoflurane
Enflurane
Halogenated anaes:

11. Ideal Properties of Inhalation Anaesthetic Agents
Rapid onset and recovery
Producing analgesia, amnesia and hypnosis
With good hemodynamic stability
Have few side effects
Have few interactions with other medications

12. Mechanism of Action Interaction with protein receptors
Volatile A – increase GABA and Glycine
( inhibitory neurotransmitters)

13. MAC(minimum alveolar concentration)
A measure of potency of inhaled anesthetics
Used to compare the potency of inhalational anesthetics
MAC is the concentration necessary to prevent responding in 50% of population.
MAC is the “gold standard” for measuring anesthesia!!!!!!!!!!!!!!!!!!!!
MINIMUM ___ ALVEOLAR_____ CONCENTRATION

14. Factors Increasing MAC
Age: highest MAC in infants (6-12 months)
Hyperthermia
Chronic alcoholism
CNS stimulants (cocaine)

15. Factors Decreasing MAC
Increase in age and prematurity
Hypothermia
Opioids
Barbiturates
Alpha 2 blockers
Calcium channel blockers
Acute alcohol intoxication
Pregnancy

16. Factors do not affect MAC
Hypocarbia
Hypercarbia
Gender
Thyroid function
Hyperkalemia

17. Factors that speed induction with inhalational agents
Increasing the delivered concentrations of anesthetics
High flow with the breathing circuit
Increasing the minute ventilation

18. Factors that slow the onset of volatile induction
Increase in cardiac output
Decrease minute ventilation
High anesthetic lipid solubility
Low flow within the breathing circuit

19. Pathway for General Anesthetics
Partial Pressure in brain quickly equilibrates with partial pressure in arterial blood which has equilibrated with partial pressure perused alveoli. Furthermore, the DEPTH of anesthesia induced by an inhaled anesthetic depends primarily on the PARTIAL PRESSURE!!! Of the anesthetics in the brain, and the rate of induction and recovery from anesthesia depends on the rate of change of partial pressure in the brain.
 These drugs are small lipid-soluble molecules that cross the alveolar membrane easily. Move into and out of the blood based on the partial pressure gradient.

20. General Actions of Inhaled Anesthetics
Respiration
Depressed respiration and response to CO2
Kidney
Depression of renal blood flow and urine output
Muscle
High enough concentrations will relax skeletal muscle
General anesthetics work by altering the flow of sodium molecules in to nerve cells or neurons through the cell membrane. Exactly how they do this is not understand since the drug apparently does not bind

21. Cont’ Cardiovascular System Central Nervous System
Generalized reduction in arterial pressure and peripheral vascular resistance.
Isoflurane maintains CO and coronary function better than other agents
Central Nervous System
Increased cerebral blood flow and decreased cerebral metabolism

22. Nitrous Oxide Inhaled Anesthetics widely used Potent analgesic
Produce a light anesthesia
Do not depress the respiration/vasomotor center
Used ad adjunct to supplement other inhalationals

23. Halothane Inhaled Anesthetics non-flammable 20% metabolism by P450
induction of hepatic microsomal enzymes
Myocardial depressant (SA node), sensitization of myocardium to catecholamines - arrhythmia 90

24. Halothane Transient hepatic damage Liver necrosis In repeated exposure
Inhaled Anesthetics
Halothane
Transient hepatic damage
Liver necrosis
In repeated exposure
Immunosensititation

25. Malignant Hyperthermia
Malignant hyperthermia (MH) is a pharmacogenetic hypermetabolic state of skeletal muscle induced in susceptible individuals by inhalational anesthetics and/or succinylcholine.
114

26. Malignant Hyperthermia
Signs: tachycardia, tachypnea, metabolic acidosis, hyperthermia, muscle rigidity, sweating, arrhythmia
May be fatal
Treated with dantrolene

27. Enflurane Rapid, smooth induction and maintenance
Inhaled Anesthetics
Enflurane
Rapid, smooth induction and maintenance
2-10% metabolized in liver
Introduced as replacement for halothane 27

28. Isoflurane smooth and rapid induction and recovery
Inhaled Anesthetics
Isoflurane
smooth and rapid induction and
recovery
very little metabolism (0.2%)
no reports of hepatotoxicity or renotoxicity
most widely employed

29. Anesthetics divide into 2 classes
Inhalation Anesthetics
Gasses or Vapors
Usually Halogenated
Intravenous Anesthetics
Injections
Anesthetics or induction agents

30. Ideal properties of intravenous anesthetic agents
Rapid onset and recovery
Producing analgesia, amnesia and hypnosis
With good hemodynamic stability
Have few side effects
Have few interactions with other medications

31. Intravenous Induction Agents
Commonly used IV induction agents
Propofol
Thiopental sodium
Ketamine

32. Organ Effects
Most decrease cerebral metabolism and intracranial pressure
Most cause respiratory depression
May cause apnea after induction of anesthesia
118

33. Cardiovascular Effects
Barbiturates, benzodiazepines and propofol cause cardiovascular depression.
119

34. Induction dose 3-6mg/kg IV
Thiopental sodium
rapid onset (20 sec)
short-acting
Induction dose 3-6mg/kg IV
117

35. Effect terminated not by metabolism but by redistribution
Thiopental sodium
Effect terminated not by metabolism but by redistribution
repeated administration or prolonged infusion approached equilibrium at redistribution sites
Build-up in adipose tissue = very long emergence from anesthesia

36. Side effects Hypotension Direct myocardial depression apnoea
Thiopental sodium
Side effects
Hypotension
Direct myocardial depression
apnoea
Peripheral dilatation
airway obstruction
Tachycardia
Decrease mean arterial pressure

37. Propofol Short-acting agent used for the induction
maintenance of GA and sedation
Onset within one minute of injection
Induction dose mg/kg IV

38. metabolised by conjugation in the liver Side-effect
Propofol
metabolised by conjugation in the liver
Side-effect
pain on injection
hypotension
transient apnoea following induction
Myocardial depression
Peripheral vasodilatation

39. Ketamine usually stimulate rather than depress the circulatory system.
Has sympathomimetic effects result in:
Increase in cardiac output
Increase MAP
Increase HR
Increase ICT
Increase IOP
Bronchodilation
Induction dose 1-2 mg/kg IV

40. Midazolam Benzodiazepine provide: Anxiolysis Sedation Amnesia
In high dose produce unconsciousness
Induction dose mg/kg IV

41. Opioids Pethedine, phyntanil, suphyntanil, morphine
High dose have vagolitic affect such as:
Bradycardia
Vasodilation
Histamine release
Except meperidine it is a sympathomimetic

42. Ketamine
Analgesic
dissociative anesthesia, eyes open, reflexes intact, purposeless but coordinated movements

43. Stimulates sympathetic nervous system
Ketamine
Stimulates sympathetic nervous system
Psychomimetic – “emergence reactions”
vivid dreaming extracorporeal (floating "out-of-body") experience misperceptions, misinterpretations, illusions
may be associated with euphoria, excitement, confusion, fear
124

44. General anesthesia
Induction
Maintenance

45. Induction intravenous inhalational Faster onset
avoiding the excitatory phase of anaesthesia
inhalational
where IV access is difficult
Anticipated difficult intubation
patient preference (children)

46. Maintenance In order to prolong anaesthesia for the required duration
breathe to a carefully controlled mixture of oxygen, nitrous oxide, and a volatile anaesthetic agent
transferred to the patient's brain via the lungs and the bloodstream, and the patient remains unconscious

47. Maintenance
Inhaled agents are supplemented by intravenous anaesthetics, such as opioids (usually fentanyl or morphine)

48. What is Balanced Anesthesia?
Use specific drugs for each component
1. Sensory
N20, opioids, ketamine for analgesia
2. Cognitive
Produce amnesia, and preferably unconsciousness
inhaled agent
IV hypnotic (propofol, midazolam, diazepam, thiopental)
3. Motor
Muscle relaxants 48

49. Simple Combinations Morphine Propofol N2O Sevoflurane
Relaxant of choice 49

50. Simple Combinations Fentanyl Thiopental sodium N2O Halothane
Relaxant of choice 50

51. SUMMARY

52. Anesthetics divide into 2 classes
Inhalation Anesthetics
Gasses or Vapors
Usually Halogenated
Intravenous Anesthetics
Injections
Anesthetics or induction agents

53. Inhalation Anesthetics
Nitrous oxide
Halothane
Isoflurane
Sevoflurane
Enflurane
Halogenated anaes:

54. Intravenous anesthetics
Thiopental sodium
Propofol
ketamine

55. Induction intravenous inhalational Faster onset
avoiding the excitatory phase of anaesthesia
inhalational
where IV access is difficult
Anticipated difficult intubation
patient preference (children)

56. Question
Compare the pharmacologicl effects of thiopentone sodium, propofol, and ketamine